Predictors of mortality and morbidity in critically ill COVID‐19 patients: An experience from a low mortality country

Abstract Background and Aims Clinical characteristics and factors associated with mortality in patients admitted to the intensive care unit (ICU) in countries with low case fatality rates (CFR) are unknown. We sought to determine these in a large cohort of critically ill COVID‐19 patients in Qatar and explore the early mortality predictors. Methods We retrospectively studied the clinical characteristics and outcomes in patients admitted to the ICU at the national referral hospital for COVID‐19 patients in Qatar. Logistic regression analysis was used to determine factors associated with mortality. Results Between March 7 and July 16, 2020, a total of 1079 patients with COVID‐19 were admitted to the ICU. The median (IQR) age of patients was 50 (41–59) years. Diabetes (47.3%) and hypertension (42.6%) were the most common comorbidities. In‐hospital mortality was 12.6% overall and 25.9% among those requiring mechanical ventilation. Factors independently associated with mortality included older age ([OR]; 2.3 [95% CI; 1.92–2.75] for each 10‐year increase in age, p < 0.001), chronic kidney disease (OR; 1.9 [95% CI; 1.02–3.54], p = 0.04), active malignancy (OR; 6.15 [95% CI; 1.79–21.12], p = 0.004), lower platelet count at ICU admission (OR; 1.41 [95% CI; 1.13–1.75] for each 100 × 103/µl decrease, p = 0.002), higher neutrophil‐to‐lymphocyte ratio at admission (OR; 1.01 [95% CI; 1–1.02] for each 1‐ point increase, p = 0.016), higher serum ferritin level at admission (OR; 1.05 [(95% CI; 1.02–1.08] for each 500 µg/L increase, p = 0.002), and higher serum bilirubin level at admission (OR; 1.19 [95% CI; 1.04–1.36] for each 10 μmol/L increase, p = 0.01). Conclusions The mortality rate among critically ill COVID‐19 patients is low in Qatar compared to other countries. Older age, chronic kidney disease, active malignancy, higher neutrophil‐to‐lymphocyte ratios, lower platelet counts, higher serum ferritin levels, and higher serum bilirubin levels are independent predictors of in‐hospital mortality.


Conclusions:
The mortality rate among critically ill COVID-19 patients is low in Qatar compared to other countries. Older age, chronic kidney disease, active malignancy, higher neutrophil-to-lymphocyte ratios, lower platelet counts, higher serum ferritin levels, and higher serum bilirubin levels are independent predictors of in-hospital mortality.

| INTRODUCTION
Coronavirus disease-19  primarily affects the respiratory system, though numerous other organs may be involved. 1 Case fatality rate (CFR) varies significantly among different countries ranging from as low as 0.05% in Singapore to around 8% in Mexico. 2 Higher mortality in persons with confirmed COVID-19 is associated with older age and the presence of comorbidities, such as diabetes mellitus type 2, hypertension, and impaired kidney function. 1,2 However, demographic differences and the burden of comorbidities likely do not fully account for the vastly different case fatality rates in various countries, and other hosts, pathogen, or environmental factors may play a role. Access to care, particularly early hospital and intensive care unit (ICU) admission are plausible hypotheses that may affect mortality in these patients.
The first case of SARS-CoV-2 infection in Qatar was diagnosed on February 28, 2020, in a returning traveler. The first locally acquired case was diagnosed on March 7, 2020. Qatar has one of the highest infection rates per capita in the world but has also witnessed one of the lowest case fatality rates. 2 With a population of approximately 2.8 million persons, Qatar has recorded only 246 deaths among 145,672 patients (0.17%) by October 2021. 3 Patients who require intensive care have significantly higher mortality, ranging from 26% to 97% in various countries. [4][5][6][7][8][9][10][11] While demographic characteristics and the presence of comorbidities are associated with higher mortality in patients admitted to the ICUs, the wide variation in mortality rate is not fully explained by these differences alone. These varied case fatality rates, for the same disease COVID-19, are probably not only because of the variance by virus or host but because of various environmental factors like the sudden surge of cases and nonavailability of resources and early access to critical care for all deserving cases. Our current knowledge is derived largely from countries with a high case fatality rate and predictors of mortality may be different in countries with a low case fatality rate.
In this study, we aim to describe the clinical characteristics and the complete outcomes of a large cohort of critically ill COVID-19 patients from a national referral hospital of Qatar and to explore the early predictors of in-hospital mortality among this cohort.

| Settings
This study was conducted at Hazm Mebaireek General Hospital (HMGH), the main referral center for COVID-19 treatment in Qatar.
We retrospectively analyzed the data of patients with reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections who needed admission to the ICU between March 7 and July 16, 2020. The outcome data were collected up to August 18, 2020

| Inclusion/exclusion criteria
We included adult patients (18 years of age or older) admitted to HMGH ICU with a confirmed diagnosis of COVID-19 and complete outcome data, either discharge from hospital or mortality. Patients who stayed for less than 24 h in the ICU were excluded. ICU stay of at least 24 h is used to show any meaningful interventions from critical care which altered patients outcomes; if they die less than 24 h, it is probably more because of the ineffective support from prehospital care or already very sick at admission, or if discharged within 24-h, likely that they did not require ICU care at all from the beginning, hence 24-h cutoff limit.

| Data collection
Patient data, including sociodemographic information, clinical data, and laboratory data, were obtained from the electronic medical records. The primary outcome was in-hospital mortality. We collected data on the incidence of complications including venous thromboembolism, rhabdomyolysis, secondary infection and bleeding, and the requirement of organ support including invasive mechanical ventilation (IMV), vasopressor therapy, renal replacement therapy (RRT), and ECMO. Tracheostomy procedures were also captured.

| Statistical analysis
Qualitative data are presented as counts with percentages and compared using the χ 2 test or Fisher's exact test, while quantitative data are presented as medians with interquartile range compared using the Mann-Whitney test. Potential predictor variables were

| RESULTS
During the study period, 1082 cases were admitted to ICU with COVID-19 and three were excluded as the length of stay in ICU was less than 24 h, hence we retrospectively analyzed the data of the re-  (Table 1) Note: Continuous data are presented as median (interquartile range) and categorical data are presented as frequency (percentage).
Abbreviations: BMI, body mass index; PaO 2 /FiO 2 ratio, arterial oxygen partial pressure divided by the fraction of inspired oxygen; SOFA, sequential organ failure assessment.  11 In the USA, a mortality rate of 31%-50% in critically ill COVID-19 patients and 36%-88% in patients who required IMV has been reported. [4][5][6] In Europe, the reported mortality in critically ill COVID-19 patients ranged from 32% to 49%. [13][14][15] In a large randomized controlled trial that examined the benefit of dexamethasone for reducing mortality among COVID-19 patients, mortality among patients receiving IMV was 29.3%. 16 A systematic review and meta-analysis of 24 studies, including 10,150 patients with complete ICU data, found a pooled ICU mortality rate of 41.6%. 17 A possible explanation of the lower mortality in the current study might be the higher percentage of steroid usage since the initial phases of the pandemic, which was later proven beneficial by randomized controlled trials. 16,18 In the current study, 85.6% of patients research is needed to explore whether genetic or environmental factors may explain such differences in disease outcomes.

T A B L E 2 Clinical interventions provided to the patients during their critical illness
In the current study, hypertension and diabetes mellitus were the most common comorbidities among critically ill COVID-19 patients (47.3% and 42.6%, respectively). The most common comorbidities in previous studies were also hypertension and diabetes mellitus. 5,10,15,16,19,20 The association of these diseases with mortality varied among reported literature, with some studies suggesting systemic hypertension is significantly associated with mortality 11,[20][21][22] and others associating diabetes with mortality. [23][24][25] Despite being more common in the patients who died in our study cohort, hypertension and diabetes were not independently associated with higher mortality after adjustment for other confounders. and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

DATA AVAILABILITY STATEMENT
The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.